The present invention relates to a series of amino acid amides having anti-tumor activity, many of which are novel compounds, and provides a pharmaceutical composition for the treatment of tumors comprising these amino acid amides, as well as a method of treating tumors and immune deficiencies using them.
A number of compounds of the amino acid type have been proposed for use as anti-tumor agents. For example, Umezawa et al. [J. Antibiotics 29(8), 857-859 (1976)] disclose a compound called "bestatin", whose systematic name is [(2S, 3R)-3-amino-2-hydroxy-4-phenylbutanoyl]-L-leucine, and which is said to exhibit host-mediated anti-tumor activity; however, the structure of this compound differs markedly from that of the compounds of the present invention. U.S. patent application Ser. No. 597,817, filed Apr. 9, 1984, now U.S. Pat. No. 4,545,942 likewise discloses a series of amino acid derivatives having anti-tumor activities, but again the structure of these compounds is markedly different from that of the compounds of the present invention.
Compounds which may be represented by the formula: ##STR2## are disclosed in Chemical Abstracts, 98(23) 198680m (1983) (R represents an isopropyl group), Chemical Abstracts, 98(25) 215947Y (1983) (R represents a sec-butyl group) and Chemical Abstracts, 93(15) 150614n (1980) (R represents a benzyl group). Compounds of formula: ##STR3## (in which Z represents a hydrogen atom, a nitro group, a chlorine atom or a methoxy group) are described in Analytical Chemistry, 56, 958-962 (1984). However, it is not disclosed that the compounds of the aforementioned Chemical Abstracts or of the Analytical Chemistry article have any therapeutic activity or value; all of these compounds are disclosed in the context of their use in analytical chemistry or in chemical synthesis.
We have now discovered that the compounds disclosed in the aforementioned Chemical Abstracts and the Analytical Chemistry article, as well as a group of closely related compounds, have excellent immunoregulatory and anti-tumor activities and are thus of potential value in the treatment of infections and of various malignant tumors, both in humans and in other animals.